City of Hope researchers have moved a step closer toward customizing cancer treatment for children based on their genetic makeup to reduce the risk of therapy-related heart disease later in life.

The research team released results from their major study of pediatric cancer patients at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago on May 20. The findings, highlighted in a press conference, associate the risk of congestive heart failure in childhood cancer survivors with common mutations in two specific genes as well as with the total amount of chemotherapy received during treatment.

Smita Bhatia led a study with implications for future cancer treatment options. (Photo by Darrin S. Joy)

Smita Bhatia, M.D., M.P.H., chair of City of Hope’s Department of Population Sciences and director of the Center for Cancer Survivorship, led the study of nearly 500 childhood cancer survivors to better understand the factors that increase a cancer patient’s risk of developing long-term cardiovascular problems.

The research team showed a direct relationship between higher doses of anthracyclines, a standard chemotherapy, and increased risk of congestive heart failure. They also found that patients with particular forms of two genes — carbonyl reductase 1 and 3, also known as CBR1 and CBR3 — had an increased risk of cardiovascular problems when taking the chemotherapy drugs, regardless of dosage.

CBR1 and CBR3 break down anthracyclines into other compounds that can damage the heart.

“Studies show that up to 60 percent of those patients treated with anthracyclines demonstrate some sign of cardiomyopathy, which is a weakening of the heart muscle, so it is important for us to find methods to mitigate these risks to long-term survivorship,” said Bhatia. “Based on our findings and additional studies, we can develop a personalized approach to treatment that addresses the genetic and medical factors that may impact our patients.”

Cardiovascular disease is one of many long-term health issues that survivors of childhood cancers may face after their cancer is cured. Anthracyclines are standard therapy for 50 to 60 percent of childhood cancer patients, although studies had already shown the drugs to have some relationship with the risk of developing congestive heart failure.

This study showed that each 100 mg/m2 dose of anthracyclines nearly doubled the risk for developing congestive heart failure. Gender matters, also: Girls in the study had a 65 percent higher risk of heart problems due to anthracyclines. Patients whose hearts were exposed to radiation during therapy were at three times higher risk than others. Most importantly, among patients who received lower doses of anthracyclines, Bhatia noted that patients with certain forms of the CBR1 and CBR3 genes fared worse.

With these findings in mind, the research team suggested that physicians in the future may consider altering treatment plans for certain pediatric cancer patients who are found to carry the specific forms of CBR1 and CBR3.

The National Institutes of Health, the Leukemia & Lymphoma Society and the Lance Armstrong Foundation funded the research.